Restoration of rhythmic slow activity (θ) in the subcortically denervated hippocampus by fetal CNS transplants

Abstract

Solid pieces of the fetal septal region (SG) or hippocampus (HPC) were implanted in a cavity formed by aspiration of the fimbriafornix (FF) and the overlying cingulate cortex on one side in adult rats. In other lesioned animals cell suspensions obtained from the fetal septal area (SS) or the locus coeruleus region of the brainstem (LC) were injected stereotaxically into the deafferented host hippocampus. Six to 9 months after transplantation the animals had chronic recording electrodes implanted into both hippocampi. EEG and unit activity were monitored during running in a wheel, drinking and immobility. Unilateral fimbria-fornix lesions abolished rhythmic slow activity (RSA or theta, θ) in the ipsilateral hippocampus and no recovery was seen up to 9 months later in either the control FF-lesioned animals or in the rats with LC suspension grafts. Recovery of RSA, however,was observed in all animals with solid septal grafts and in some rats with solid HPC grafts. Similar to normal rats, RSA was present only during running and absent during drinking and sitting still. Coherence measurements of RSA between the transplanted and intact hemispheres resulted in high values (0.70–0.95). Concurrent with RSA, interneurons and granule cells in the host hippocampus fired rhythmically at RSA frequency (6–9 Hz). The depth profile and the antero-posterior distribution of the power of RSA correlated with the amount and distribution of the graft-induced acetylcholinesterase-positive reinnervation of the host hippocampus. In contrast to the animals with solid septal grafts, placed within the FF lesion cavity, the rats with intrahippocampal septal suspension grafts displayed only short duration bursts of RSA, and mainly during immobility. Based on these findings it is suggested that at least a proportion of the RSA ‘pacemaker’ cells of the host septum survives the transection of the fimbria-fornix fibers and that a graft of fetal septal or hippocampal tissue implanted into the lesion cavity may be capable of relaying this pacemaker activity to the host hippocampus. This effect may be due to the ability of the grafted tissue to promote the regeneration of new, direct or indirect, septo-hippocampal connections across the lesion cavity.